Tin derivatives of sulfosalicylic acids



United States Patent 3,201,432 TIN DEVATIVES OF SULFOSALICYLIC ACIDS.Iohn R. Ileebrick, Roselle Park, N.J., assignor, by mesne assignments,to M. 8; T. Chemicals Inc., New York, N.Y., a corporation of Delaware NoDrawing. Filed Dec. 15, 1961, Ser. No. 159,738

16 Claims. '(Cl. 260-429.'7)

together sulfosalicylic acid having the formula [soar m lsosmbria I withmoles of (R Sn) O for each mole of said acid, and heating said mixturethereby completing reaction to form I 3(S11Ra) x yla b I GO OSnRswherein a, b, x, and y are each independently selected from the groupconsisting of 0 and 1; wherein a+b:1; and x+y:1.

Sulfosalicylic acid may be commercially available as3-carboxy-4-hydroxybenzenesulfonic acid or as the isomer3-hydroxy-4-carboxybenzenesulfonic acid, or as a mixture thereof. Bothforms of the acid, which may commonly be prepared by the sulfonation ofsalicylic acid and which may as commercially available exist in the formof the dihydrate, may be represented by the formula OOH wherein a and bare each selected from the group consisting of 0 and 1 and w+b:l. When ais 1 and b is O, the formula becomes I and when a is O and b is l, theformula becomes II.

COOH

I C O OH The compounds (R Sn) O which may be employed to form the novelproducts of this invention may include those wherein R may be ahydrocarbon radical which may be inertly substituted. An inertlysubstituted hydrocarbon radical is one which contains no active groupswhich may react with the other components of the reaction system.Typically R may be selected from the group consisting of alkyl, aryl,alkenyl, alkynyl, aralkyl, alkaryl, cycloalkyl, cycloalkenyl,cycloalkynl, etc.

Typical alkyls may include methyl, ethyl, propyls, butyls, amyls,hexyls, heptyls, octyls, etc. Typical aryls may include phenyl,naphthyl, etc. Typical alkenyls may include vinyl, allyl, l-butenyl,etc. Typical alkynyls may include ethynyl, propynyls, butynyls, etc.Typical aralkyls may include benzyl, styryl, w-phenyl propyl, etc.Typical alkaryls may include tolyl, xylyl, etc. Typical cycloalkyls mayinclude cyclohexyl, cycloheptyl, methylcyclohexyls, etc. Typicalcycloalkenyls may include cyclohexenyl, cycloheptenyl, cyclohexadienyl,etc. It will be found that the nature of R will have little or no effecton the process for preparing the compositions of this invention.

In one preferred embodiment, R may be a hydrocarbon radical selectedfrom the group consisting of lower alkyl radicals and the phenylradical.

It will be apparent to those skilled in the art that certain of thecompounds (R Sn) O may exist in equilibrium, in the presence of smallamounts of water, with the corresponding hydroxide viz.:

Furthermore, it will also be apparent that certain of the compounds (RSn) O may be prepared and commonly available (because of the aboveequilibrium) as the hydroxide, R SnOH. For example, the methyl, ethyl,and phenyl derivatives are commonly available as the hydroxide, e.g.triphenyltin hydroxide, rather than as the oxide. Thus, the formula (RSn) O may be taken to include the equivalent hydroxide R SnOH. Since theformer compound contains two R Sn groups per molecule and the lattercontains one, it will be necessary, when the hydroxide is used in placeof the oxide that the molar quantity of the tin compound be doubled sothat the same molar ratio of R Sn groups to sulfosalicylic acid will bemainatined.

Illustrative compounds (R Sn) O may include bis(trin-butyltin) oxide,bis(tri-n-amyltin) oxide, bis(tri-nhexyltin) oxide, bis(tri-n-propyltin)oxide, bis (tri-n-octyL tin) oxide, trimethyltin hydroxide, triethyltinhydroxde, triphenyltin hydroxide, etc.

Preparation of the novel reaction products of this invention may beefiected by reacting sulfosalicylic acid with the compound (R Sn) O.Reaction of these compounds may be effected by mixing the reactants andheating the mixture preferably to at least about C. and preferably to-180 C. at which temperature the water formed as by-product may bevolatilized. The reaction mixture may be maintained at this temperaturefor at least about 30 minutes, and preferably 60-90 minutes. Reactionmay be conducted under vacuum if desired.

a During the course of the reaction in its preferred embodiment, as theevolved water is volatilized, the mixture may become progressively moreviscous until at the end of 60-90 minutes, the mass may approach thesolid state.

If desired, the reaction may be conducted at lower temperature and undermore readily controlled conditions by use of a diluent, preferably oneboiling above 100 C.- 110 C. Preferably the diluent may (a) be a liquidwhich forms an azeotropic mixture with water, thereby driving thereaction to completion, (b) be solvent for the product, and (e) have aboiling point of about 110 C.-200 C. Typical of the diluents which maybe employed may be toluene, xylenes, decalin, cymenes, cumene,et-hylbenzene, t-butyl benzene, n-butyl ether, amyl alcohols, etc. Otherappropriate solvents including aliphatic or aromatic hydrocarbons,alcohols, ethers, etc. may be employed. When a diluent-solvent isemployed, e.g. benzene, the temperature of the reaction mixture may bee.g. 70 C. which may correspond to the boiling point of thebenzene-water azeotrope. In the practice of this invention, lowertemperatures may be employed but the reaction time will be greatlyincreased thereby.

When the reaction is conducted in the presence of diluent, it may beconducted under reflux until the theoretical amount of water isrecovered. The diluent may then be removed by distillation, preferablyat reduced pressure of typically 20-50 mm. Hg.

The desired reaction product may be formed in the reaction vessel as theby-product water is removed therefrom. As so prepared it may approach100 purity. It may be in the form of a liquid which on cooling maybecome a thick viscous liquid or pasty mass or a hard rock-like solid.

When the ratio of reactants is one mole of sulfosalicylic acid for 0.5mole of (R Sn) O, the reaction may be as follows:

[SOaHhH 1 S Ib n %(RsSn)2 I C O OH [SOa L b 1 3 ]b n AH2 l COOSnRa Thisproduct may be isolated or if desired it may be further reacted with anadditional 0.5 mole of (R Sn) O as follows:

If desired, the sulfosalicylic acid may be reacted with an equimolaramount of (R Sn) O to yield the last noted product.

The novel compositions of matter of this invention formed by thereaction of sulfosalicylic acid with a compound having the formula (RSn) O may have the formula [S|O;(SnR3) H mn,

CO OSIlR3 wherein R is a hydrocarbon radical; a, b, x, and y are numberseach independently selected from the group consisting of 0 and 1; a+b=1;and x+y=l.

It is a feature of this invention that the novelcompounds, especiallythose containing R groups having less than about seven carbon atoms, areparticularly characterized by their unexpectedly high melting point.Typical of these preferred compounds may be noted those wherein R may bemethyl, ethyl, n-propyl, i-propyl, nbutyl, i-butyl, t-butyl, n-arnyl,i-amyl, n-hexyl, i-hexyl, etc. In the preferred embodiment, R may be then-butyl radical. Another preferred compound may be that wherein R is then-propyl radical.

The novel products of this invention, and particularly the preferredproducts wherein R contains less than about seven carbon atoms, may becharacterized by their unexpectedly high melting point. The reactionproduct of either one mole or two moles of bis(tri-n-butyltin) oxide andtwo moles of sulfosalicylic acid for example melts above 260 C.; thecorresponding phenyl compound melts at about the same temperature. Thesecompounds are stable to temperatures which may approach 300 C. or

more.

Preparation of the novel products of this invention may be observed byinspection of the following examples wherein the parts are by weightunless otherwise indicated.

EXAMPLE 1 4Ha)a l2 2 2 HO HO- 500 parts (2 moles) of sulfosalicylic aciddihydrate may be charged to a reactor fitted with stirrer, condenser,and thermometer. 2500 parts of toluene may then be added and the mixturestirred for 10 minutes during which time the acid may not go completelyinto solution. The mixture may be heated to C. and 596 parts (1 mole) ofbis (tri-n-butyltin) oxide added dropwise over thirty minutes. As themixture is heated under reflux, water may be distilled out starting atabout 93 C. The theoretical water, parts (18 parts from the reactionproper and 72 parts from the acid dihydrate), may be recovered as thetoluene is distilled off.

The product on cooling to room temperature may be found to be a whiterock-like solid. It may be slurried with petroleum ether, filtered,washed with petroleum ether, and air dried. Melting point may be above260 C.

The product upon cooling to room temperature may be found to have thefollowing analysis.

Sn: Percent Calculated 23.3 Found 22.94

Calculated 6.3 Found 6.77

EXAMPLE 2 l( 4H9)s l2 2 1110 HO HO- ($0011 doosmc nm 179 parts (0.3mole) of bis(tri-n-butyltin) oxide may be charged to an open reactionvessel. The oxide may then be heated to 60 C. at which temperature 153parts (0.6 mole) of sulfosalicylic acid dihydrate may be added withagitation. On heating with agitation, the mixture may begin to foam atabout 95 C. As heating is effected over 30 minutes, the mass becamecompletely liquid at 100 C. and as water was boiled off, the massbecame.

pasty as the temperature aproached 115 C. after 60 minutes. The mass,which solidified on cooling to room temperature, was pulverized,slurried in petroleum ether, filtered, washed with water, filtered,Washed with petroleum ether, and dried. The dried solid product,obtained in amountv of 294 parts, having a melting point above 260 C.,

on analysis may be found to have substantially the same analysis as theproduct of Example 1.

EXAMPLE 3 sour 'no l( 4 e)aSn] O V doon SOaSlKCrHflg do osmoni 500 parts(2 moles) of sulfosalicylic acid dihydrate may be charged to a reactorfitted with stirrer, condenser, and thermometer. 3000 parts of toluenemay then be added and the mixture stirred for 10 minutes during whichtime the acid may not go completely into solution. The mixture may beheated to 80 C. and 1192 parts (2 moles) of his (tri-n-butyltin) oxideadded dropwise over thirty minutes. The mixture was heated under reflux.Water was distilled out starting at 93 C. The theoretical water 108parts (36 parts from the reaction proper and 72 parts from the aciddihydrate) may be recovered as the toluene is distilled ofl.

The product on cooling to room temperature may be found to be a whiterock-like solid. It may be washed with petroleum ether, filtered, andair dried. Melting point may be above 260 C.

EXAMPLE 4 HO 7 a 1)aSn] O boon 2 scan boosmonarm 500 parts (2 moles) ofsulfosalicylic acid dihydrate may be charged to a reactor fitted withstirrer, condenser, and thermometer. 1500 parts of toluene may then beadded and the mixture stirred for 10 minutes during which time the acidmay not go completely into solution. The mixture may be heated to 80 C.and 512 parts (1 mole) of bis(tri-n-propyltin) oxide added dropwise overthirty minutes. The mixture was heated under reflux. Water was distilledout starting at 93 C. The theoretical Water, 90 parts (18 parts from thereaction proper and 72parts from the acid dihydrate), may be recoveredas-the toluene is distilled off.

The product on cooling to room temperature may be found to be a whiterock-like solid. It may be washed I point may be above 260 C.

and thermometer.

EXAMPLE 5 470011 COOSn(CaH5)s 500 parts (2 moles) of sulfosalicyh'c aciddihydrate may be charged to a reactor fitted with stirrer, condenser,and thermometer. 2000 parts of toluene may then be added and the mixturestirred for 10 minutes during which time the acid may not go completelyinto solution. The mixture may be heated to C. and 716 parts (1 mole) ofbis(tri-n-phenyltin) oxide added dropwise over thirty minutes. Themixture was heated under reflux. Water was distilled out starting at 93C. The theoretical water, parts (18 parts from the reaction proper and72 parts from the acid dihydrate), may be recovered as the toluene isdistilled ofi".

The product on cooling to room temperature may be found to be a whiterock-like solid. It may be washed with petroleum ether, filtered, andair dried. Melting point may be above 275 C.

EXAMPLE 6 2 V S03H 2 $03K s 17)aS ]20 1120 H0 H0- OOH (EOOSIKCBI'IUM 500parts (2 moles) of suliosalicylic acid dihydrate may be charged to areactor fitted with stirrer, condenser, 2000 parts of toluene may thenbe added and the mixture stirred for 10 minutes during which time theacid may not go completely into solution. The mixture may be heated to80 C. and 932 parts (1 mole) of bis(trin-octyltin) oxide added dropwiseover thirty minutes. The mixture was heated under reflux. Water wasdistilled out starting at 93 C. The theoretical water, 90 parts (18'parts from the reaction proper and 72 parts from the acid dihydrate),may be recovered as the toluene is distilled off.

The product on cooling to room temperature may be found to be a whitepasty mass. It may be washed with petroleum ether, filtered, and airdried.

EXAMPLE 7 03K S|O3H [041103811120 m0 HO- HO- 6 COOH OOS11(C4H9)3 500parts (2 moles) of sulfosalicylic acid dihydrate may be charged to areactor fitted with stirrer, condenser, and thermometer. 2500 parts oftoluene may then be added and the mixture stirred for 10 minutes duringwhich time the acid may not go completely into solution. The mixture maybe heated to 80 C. and 596 parts (1 mole) of bis(tri-n-butyltin) oxideadded dropwise over thirty minutes. As the mixture is heated underreflux, water maybe distilled'out starting at about 93 C. Thetheoretical water, 90 parts (18 parts from the reaction proper and 72parts from the acid dihydrate), may be recovered as the toluene isdistilled off.

The product on cooling to room temperature may be found to be a Whiterock-like solid. It may be slurried with petroleum ether, filtered,washed with petroleum ether, and air dried. Melting point may be above260 C.

It is a feature of the novel products of this invention that they areparticularly characterized by their high melting point especially whenthe R group contains less than about seven carbons. Because of thisfact, together with their extreme stability when subjected to hightemperature for extended periods of time, they may find use in hightemperature and/or high pressure fluids.

It is also a feature of these novel compounds that they arecharacterized by their unexpected microbiological activity. It may bepossible to use these novel compounds to obtain sanitary material whichis substantially completely odor free. Because of the high melting andboiling point of these compounds, and their extremely low volatility,they may be retained on e.g. cloth or other textile for an extendedperiod of time. They are characterized by their extremely low vaportoxicity because of low vapor pressure at ambient temperature. Suchcompounds, typically that formed by the process of Example 1 supra maybe dissolved in volatile solvents such as methanol to form solutionwhich may be e.g. sprayed onto textiles or other surfaces which are tobe rendered resistant to attack by miccroorganisms for extended periodsof time.

To illustrate the microbiological action of these materials thefollowing experiments were carried out:

The products of Examples 1 (dissolved in ethanol), 3 (dissolved inethanol) and 4 (dissolved in methanol) were tested to determine theiranti-microbial activity by adding the solutions to each of a series ofstandard nutrient broths. In each series the broths after addition ofthe compound contained 0.25, 0.5, l, 2, 4, 8, 16, 32, and 64 parts permillion of the compound. The alcohol content of each broth was below theinhibitory amount. In each series, the ample containing the minimumamount in parts per million (p.p.m.) Which was effective in controllingthe growth of the organism was noted and is tabulated below as theeffective level, together with the organisms against which it wastested.

Table l TRIBUTY'LTIN :sunnosamcrammnxnmmnn 1) Organism: Effective level,p.p.m. Penicillium funiculosum 16 Aspergillus flavus 1 Candida albicans0.5 Bacillus mycoides 0.5

Table II BIS(TRI-l1-BUTYLTIN) SULFOSALICYAT-E (EXAMPLE '3) Organism:Elfective level, p.p.m. Perzicz'llium funiculosum Aspergillus flavus 0.5Candida albicans 0.25 Staph. aureus 1 Table III TRIPROPY'LTINSULFOSALICYIJATE (EXAMPLE 4) Organism: Effective level, p.p.m.

Penicillium funiculosum 2 60 Aspergillus flavlls 0.25 Candida albicans0.25 Aerobacter aerogenes 31 Pseudomonas aerugz'nosa 31 Staph. aureus 4From inspection of these tables, it will be apparent that these novelcompositions are highly active against various types of organisms andthat this activity is obtained by use of compounds which do not possesshigh volatility. Because of low volatility, the compounds may retaintheir activity in situ for extended periods of time. Furthermore thesecompounds, because of their low lipid solubility, are of considerablylower toxicity than prior art compounds or than the intermediate oxidesfrom which they may be prepared. As a result of'the lower volatility,the vapor is low.

Although this invention has been described with reference to specificexamples, it will be apparent that various modifications may be madethereto which fall within the scope of this invention.

I claim:

1. A composition of the formula I C O OSnRa wherein a, b, x, and y areeach selected from the group tconsisting of 0 and 1; a+b=l; x+y=1; andwherein R is a hydrocarbon radical.

a 2. A composition as claimed in claim 1 wherein b=1. 3. A compositionas claimed in claim 1 wherein a=l.

i 4. A composition of the formula JO OSDRa wherein R is a hydrocarbonradical selected from the group consisting of lower alkyl radicals andphenyl radicals; a, b, x, and y, are selected from the group consistingof 0 and l; a+b=1; and x+y=1.

5. A composition of the formula wherein R is a hydrocarbon radicalselected from the group consisting of lower alkyl radicals and thephenyl rradical; x and y are selected from the group consisting of 0 and1; and x+y=1.

6. A composition as claimed in claim 5 wherein R is the n-butyl radical.

7. A composition as claimed in claim 5 wherein R is the n-propylradical.

8. A composition as claimed in claim 5 wherein y=l. 9. A composition ofthe formula 10 OSnRa 13. The process for preparing [S05 (SnRa) E -15 b(50 O SllRa which comprises mixing one mole of [S|O H],.Hh

[ 3 Ib a 14. The process for preparing compositions as claimed in claim13 wherein R is a hydrocarbon residue selected from the group consistingof lower alkyl radicals and the phenyl radical.

15. The process for preparing compositions as claimed in claim 13wherein the reaction is carried out in a diluent. V

16. The process for reacting 3carboxy-4-hydroxybenzenesulfonic acid with(R Sn) O wherein R is a hydrocarbon radical which comprises mixing3-carboxy-4-hydroxybenzenesulfonic acid with (R Sn) O, and heating saidmixture.

References Cited by the Examiner UNITED STATES PATENTS 2,864,737 12/58Fields et a1. 16722 2,873,288 2/59 Rosenberg et al. 260429.7 2,878,1553/59 Cruickshank 16722 2,892,856 6/59 Ramsden et al. 260-429.7 2,957,78510/60 Leatherland 260429.7 2,977,379 3/61 Dorfelt 260429.7

TOBIAS E. LEVOW, Primary Examiner.

1. A COMPOSITION OF THE FORMULA